A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria

• Male or female participants 18 years of age or older.
• Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis.

NOTE: The initial diagnosis must have been symptomatic multiple myeloma, although the relapsed disease did not need to be symptomatic.

• Must have had measurable disease, defined by at least 1 of the following 3 measurements:
• Serum M-protein ≥ 1 g/dL (≥ 10 g/L).
• Urine M-protein ≥ 200 mg/24 hours.
• Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum FLC ratio was abnormal.
• Participants with relapsed and/or refractory multiple myeloma (RRMM) who had received 1 to 3 prior therapies.

NOTE: population included the following 3 categories of participants:

• Participants who relapsed from their previous treatment(s) but were not refractory to any previous treatment.
• Participants who were refractory to all lines of previous treatment(s) (ie, participants who had never responded to any therapies received).
• Participants who relapsed from at least 1 previous treatment AND additionally were refractory to at least 1 previous treatment. For the purposes of this study, refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy.

A line of therapy was defined as 1 or more cycles of a planned treatment program. This may have consisted of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance was considered 1 line of therapy. Autologous and allogenic transplants were permitted.

• Must have met the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1000/mm^3 and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria were not allowed within 3 days prior to randomization.
• Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
• Calculated creatinine clearance ≥ 30 mL/min NOTE: Participants with a low creatinine clearance ≤ 60 mL/min (or ≤ 50 mL/min, according to lenalidomide prescribing information/local practice) were to receive a reduced lenalidomide dose of 10 mg once daily (QD) on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may have been escalated to 15 mg QD after 2 cycles if the participant was not responding to treatment and was tolerating the treatment. If renal function normalized (ie, creatinine clearance >60 mL/min or >50 mL/min, according to lenalidomide prescribing information/local practice) and the participant continued to tolerate this treatment, lenalidomide may then have been escalated to 25 mg QD.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Participants who received prior allogenic transplant must have had no active graft-versus-host disease.
• Female participants who:
• Were postmenopausal for at least 24 months before the screening visit, OR
• Were surgically sterile, OR
• If they were of childbearing potential must have: had a negative pregnancy test with a sensitivity of at least 25 mIU/mL within 10 to 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide; either agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal were not acceptable methods of contraception.) OR begun 2 reliable methods of birth control (1 highly effective method and 1 additional effective method) at the same time, at least 28 days before starting study treatment through 90 days after the last dose of stu